Transmembrane chemokines act as receptors in a novel mechanism termed inverse signaling

被引：25

作者：

Hattermann, Kirsten ^{[1
]}

Gebhardt, Henrike ^{[1
]}

Krossa, Sebastian ^{[2
]}

Ludwig, Andreas ^{[3
]}

Lucius, Ralph ^{[1
]}

Held-Feindt, Janka ^{[4
]}

Mentlein, Rolf ^{[1
]}

机构：

[1] Univ Kiel, Dept Anat, Kiel, Germany

[2] Univ Kiel, Inst Zool, Dept Biol Struct, D-24098 Kiel, Germany

[3] Rhein Westfal TH Aachen, Inst Pharmacol & Toxicol, Aachen, Germany

[4] Univ Med Ctr Schleswig Holstein, Dept Neurosurg, Kiel, Germany

来源：

ELIFE | 2016年 / 5卷

关键词：

HUMAN TUMORS; CELL-LINES; TNF-ALPHA; FRACTALKINE; EXPRESSION; LIGAND; CLEAVAGE; CX3CL1; CXCL16; ESTABLISHMENT;

D O I：

10.7554/eLife.10820

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The transmembrane chemokines CX3CL1/fractalkine and CXCL16 are widely expressed in different types of tumors, often without an appropriate expression of their classical receptors. We observed that receptor-negative cancer cells could be stimulated by the soluble chemokines. Searching for alternative receptors we detected that all cells expressing or transfected with transmembrane chemokine ligands bound the soluble chemokines with high affinity and responded by phosphorylation of intracellular kinases, enhanced proliferation and anti-apoptosis. This activity requires the intracellular domain and apparently the dimerization of the transmembrane chemokine ligand. Thus, shed soluble chemokines can generate auto- or paracrine signals by binding and activating their transmembrane forms. We term this novel mechanism "inverse signaling". We suppose that inverse signaling is an autocrine feedback and fine-tuning system in the communication between cells that in tumors supports stabilization and proliferation.

引用

页数：23

共 51 条

[1] The transmembrane CXC-chemokine ligand 16 is induced by IFN-γ and TNF-α and shed by the activity of the disintegrin-like metalloproteinase ADAM10 [J].